Found in many foods, this amino acid helps with depression, chronic pain, and belly fat loss. Your body uses it as a building block for important neurotransmitters and proteins. Phenylalanine offers surprising benefits, but certain people should avoid it by all means. Read on to find out if it’s right for you.

What is Phenylalanine?

Phenylalanine is an amino acid that builds proteins, neurotransmitters, and other crucial molecules in your body. We can’t make phenylalanine, which makes it an essential amino acid we need to get from food [1, 2].

Nutritional supplements can contain different forms of phenylalanine with unique mechanisms and health effects—we’ll dive into details about each one.

Structure

Source: https://commons.wikimedia.org/wiki/File:Phenylalanin(L-und_D-Phenylalanin)_V1.png

Phenylalanine molecule has 2 different forms, L- and D-phenylalanine, which are “mirror images” with the same structure. As you can see in the image above, they are only differently oriented in space [3].

L-phenylalanine is the active form that occurs naturally in a variety of foods. Your body uses it to make proteins and other molecules [4, 5].

D-phenylalanine is the synthetic form made in the lab. Your body partly converts it to the L-form or eliminates it via urine, but it also has some specific health effects discussed below [6, 7].

Supplements can contain either form or a mixture of their equal amounts, known as DLPA (DL-phenylalanine).

Snapshot

PROS

  • Helps with depression
  • May support weight loss
  • Helps with vitiligo
  • May reduce pain
  • May help with substance dependence

CONS

  • May cause nausea
  • Dangerous for people with phenylketonuria
  • Has mixed effects on blood pressure

Phenylalanine Foods

Most protein-rich foods contain decent amounts of L-phenylalanine. These include [8, 9]:

  • Eggs
  • Milk and dairy products
  • Legumes (beans and peanuts)
  • Sunflower and sesame seeds
  • Red meat and poultry
  • Fish

Eating a variety of good protein sources will grant you an optimal phenylalanine intake.

People with an inborn metabolic disorder called phenylketonuria (PKU) should avoid all foods and supplements high in phenylalanine (more details in the “Side Effects and Precautions” section) [10].

Health Benefits of Phenylalanine

How Does Phenylalanine Work?

Source: N.V. Bhagavan, Chung-Eun Ha, in Essentials of Medical Biochemistry, 2011

Joined with other amino acids, L-phenylalanine builds proteins that support the structure and delicate functions of the entire body.

L-phenylalanine converts to another amino acid, tyrosine, which further gives [11, 12]:

It also boosts the release of CCK, a hormone that reduces appetite [13].

Thanks to these complex roles, L-phenylalanine can impact mental health, cognition, skin appearance, weight control, and more.

The body can’t use the other, D form of this amino acid as a building block. Instead, D-phenylalanine combats inflammation and inhibits an enzyme that degrades your natural opioids. These opioids control pleasure, pain, immunity, and mood [14, 15].

1) Helps with Depression

L-phenylalanine enables the production of mood-boosting neurotransmitters such as dopamine and norepinephrine. Low brain levels of these chemicals often lurk behind the symptoms of depression [11, 16].

A diet devoid of phenylalanine and tyrosine may impair mood and increase irritability. According to a review of clinical data, these amino acids can help with mild to moderate depression [17, 18].

In one clinical trial with 155 depressed patients, a combination of L-phenylalanine (250 mg daily) and standard treatment was beneficial in 80-90% of the cases [19].

Blood and urine levels of phenylalanine tend to be lower in depressed patients than in healthy people. Supplementation with L-phenylalanine improved mood in 31 of 40 such patients [20].

D-phenylalanine may also enhance mood by raising natural opioids in the brain. A supplement with both forms, DL-phenylalanine (DLPA), has also shown positive results in depression [21].

DLPA (150-200 mg daily) had the same effect as an antidepressant, imipramine, in a study with 40 depressed people [22].

In 2 more clinical trials, it wiped out the symptoms of depression in 29 out of 43 patients and provided moderate improvement in 4 cases [23, 24].

However, the above studies had notable limitations we’ll discuss in “Limitations and Caveats” below.

Additionally, D-phenylalanine alone provided no benefits in 11 depressed patients. It even worsened the condition in 2 cases [25].

Summary

Evidence suggests that L-phenylalanine and DLPA may help with mild-to-moderate depression.

2) Reduces Vitiligo

Vitiligo is an autoimmune disease in which cells that make the skin pigment melanin gets destroyed. As a result, melanin content drops and parts of the skin lose color [26].

L-phenylalanine converts into melanin and acts as a natural remedy for vitiligo [27].

In a study with 70 vitiligo patients, a combination of topical (10% gel) and oral (100 mg/kg daily) L-phenylalanine showed promising results. It recovered skin color in 90% of the patients when added to standard treatment with UV light and medications [28].

Trials with over 270 vitiligo patients confirmed the beneficial effects of phenylalanine creams and supplements in combination with UV therapy [29, 30, 31].

3) May Support Weight Loss

There’s no magic pill for weight loss, but certain natural substances can boost the effects of physical activity and dietary changes.

In 2 studies with 52 women, high doses of L-phenylalanine (10 g) reduced food intake by 11-15%. The effects depended on dietary habits and the phase of the menstrual cycle. Women might respond better to appetite suppressants in the first half of the menstrual cycle (follicular phase), but more research is needed [13, 32, 33, 34].

In over 300 obese adults, supplements with L-phenylalanine significantly reduced belly fat when combined with exercise and dieting, but they didn’t cause weight loss [35, 36].

Other ingredients in these supplements – such as arginine, chromium, and inulin – have likely contributed to the results.

Pre-exercise supplementation with 3 g of L-phenylalanine enhanced fat burning in 6 volunteers. A mixture containing this amino acid showed the same results in 10 people [37, 38].

In summary, L-phenylalanine can reduce your appetite and help you burn fat.

4) May Reduce Pain

D-phenylalanine boosts your natural opioids, beta-endorphins, and enkephalins, which play a central role in pain management. Doctors have been using it as an add-on supplement for different types of chronic pain since the ‘80s, sometimes in combination with acupuncture [39].

Some doctors experimenting with alternative pain management report clinical success with phenylalanine. They pair it with electromagnetic currents (such as the ICES), dietary changes (high-protein diets), other amino acid supplements, and meditation/relaxation techniques.

Studies are few and less encouraging.

In one study of 56 patients who underwent a tooth extraction, D-phenylalanine supplementation (4 g) increased the effects of acupuncture anesthesia by 35%. It provided a 26% improvement in another study of 30 patients with lower back pain, but the authors found it non-significant [40].

Studies on rats and mice have confirmed the pain-killing effect of D-phenylalanine, alone and in combination with other drugs [41, 42].

However, it offered no significant benefits to 30 people with chronic pain. A study on monkeys also found a weak effect on pain [43, 44].

All in all, it’s still uncertain whether phenylalanine can reduce pain. It’s an inexpensive drug and may help some people, but the management of chronic pain often requires a holistic approach and multiple interventions.

5) May Combat Substance Dependence

Our internal opioids don’t just block pain signals, they regulate a deep-seated reward system in our brain that makes certain things enjoyable [45].

People dependant on synthetic opioids and other drugs have suppressed internal opioids. When they go off the drug that triggered their addiction, various withdrawal symptoms emerge. Cravings and the risk of relapse are also big issues.

Phenylalanine may help by boosting natural opioids, thus reducing the need for stronger external triggers in the long run. This mechanism could even be of use in people undergoing opioid withdrawal, which poses a huge challenge to chronic pain management [14, 46].

In a study on 20 patients struggling with alcohol withdrawal, a supplement with D-phenylalanine, 5-HTP, and glutamine greatly reduced their psychiatric symptoms and stress [47].

The effect was likely due to increased brain levels of dopamine and enkephalins.

Scientists were able to reduce alcohol addiction in mice with D-phenylalanine and hydrocinnamic acid by recovering their internal opioids [48].

According to recent research, D-phenylalanine (DPA) and N-acetylcysteine (NAC) may work in synergy to relieve addictions. NAC balances glutamate in the reward system and counteracts DPA’s dopamine stimulation. As a result, dopamine levels stay in the optimal range [49].

Clinical trials are yet to confirm the safety and efficacy of this combination.

6) May Help with Attention Disorders

L-phenylalanine helps in the formation of dopamine, which plays vital roles in mental health and attention. Low dopamine levels may trigger ADHD symptoms [50].

In a study on 44 children, those with ADHD had significantly lower blood and urine levels of phenylalanine [51].

DLPA supplement (1200 mg daily for 2 weeks) improved the symptoms such as anger, restlessness, and poor concentration in 19 adults with ADD. However, 3 months after the study finished, the beneficial effects disappeared [52].

A review of clinical trials found no significant benefits of phenylalanine for ADHD [53].

Also, D-phenylalanine failed to improve the behavior of 11 hyperactive boys [54].

Summary

Phenylalanine may help with attention disorders in adults, but the evidence is weak. Children with ADHD don’t seem to get any benefits.

Side Effects & Safety

All supplement forms were safe in clinical trials and didn’t cause significant side effects. However, L-phenylalanine did cause nausea in higher doses [13, 28, 54, 24, 23].

According to the FDA, L-phenylalanine is “generally recognized as safe” (GRAS) in foods and supplements [55].

Diabetes Risk

In 1680 young adults, increased intake of aromatic and branched-chain amino acids was associated with insulin resistance and a higher risk of diabetes. The connection was stronger in men (doubled risk) and included [56]:

Effects on Blood Pressure

There is public concern about the potential of phenylalanine to raise blood pressure, but the studies reveal mixed effects.

An observational trial with over 4K patients showed a connection between increased intake of phenylalanine and high blood pressure [57].

In one study on rats, phenylalanine slightly increased blood pressure [58].

However, no clinical trials have confirmed this effect. Phenylalanine even reduced blood pressure and protected blood vessels in multiple studies on rats [59, 60, 61, 62].

Phenylketonuria

People with a rare inborn metabolic disorder – phenylketonuria (PKU) – are unable to break down phenylalanine properly. The buildup of this amino acid, in turn, causes brain damage and cognitive impairment [63, 64, 65].

The disorder occurs due to an inherited lack of phenylalanine hydroxylase (PAH), an enzyme that converts phenylalanine to tyrosine. PAH deficiency is a milder form in which patients can metabolize small amounts of phenylalanine [66].

Phenylketonurics should follow a special low-protein diet to minimize the intake of phenylalanine. Obviously, they should steer clear of all phenylalanine supplements [67, 68].

Aspartame is an artificial sweetener that contains phenylalanine. Sugar-free items such as diet soda (and chewing gum) may contain it.

All foods and drinks with added phenylalanine or aspartame must have a warning label for people with phenylketonuria.

Besides the strict dietary regimen, scientists are developing new treatment options for this disorder, including gene therapy [69].

Drug Interactions

Phenylalanine interacts with L-DOPA, a drug for Parkinson’s disease. It hinders the transport of L-DOPA to the brain, which may cause sharp changes in a clinical response known as the “on-off” phenomenon [70].

Talk to your doctor before supplementing if you take prescription medications to avoid any potential drug interactions.

Use in Children and Pregnant Women

Children seem to tolerate phenylalanine well, but they should take it under medical supervision. It is unknown whether phenylalanine supplements are safe to take during pregnancy or while breastfeeding. Pregnant women should avoid all phenylalanine supplements until we know more about their safety. Risk of the mother developing phenylketonuria (PKU) from taking phenylalanine supplements is of the greatest concern [53, 54, 71].

Genetics

Mutations in the gene that codes for phenylalanine hydroxylase (PAH) can trigger the symptoms of phenylketonuria. In a clinical trial with 160 subjects, the SNPs EX6-96 and R243Q were the most common PAH mutations among phenylketonurics (those that develop phenylketonuria) [72].

Other common mutations in this gene have been linked to memory performance in healthy people. In a study on 600 adults, those with a specific PAH variant (”GG” in the SNP rs2037639) had worse verbal memory [73].

Limitations and Caveats

Except for vitiligo treatment, all phenylalanine benefits lack stronger clinical evidence.

This amino acid is essential for a range of our physical and mental functions, but we still have a lot to learn about phenylalanine supplementation.

Most studies on patients with depression are over 40 years old and lack placebo controls [22, 23, 24].

Studies for chronic pain and attention disorders have mixed results and don’t point to a definite conclusion [53, 40, 43].

Supplements and Reviews

Both L- and D-phenylalanine usually come in 500 mg pills. Bulk powder with L-phenylalanine is also available.

Users report positive experiences with L-phenylalanine for depression, anxiety, and mental clarity. However, many people had no benefits from this supplement, and some even experienced mood swings and headaches.

People take D-phenylalanine for chronic pain, and most of them are satisfied with the results. Others mention that supplementation improved their focus and energy.

For DL-phenylalanine supplements and user reviews, check out our DLPA article.

Formulations Overview

Still not sure which one is the best option for you? Here’s an overview of their benefits:

DepressionWeight lossPainAddictionADHDVitiligo
L-Phe
D-Phe
DLPA

*Phe=Phenylalanine

Buy

This section contains sponsored links, which means that we may receive a small percentage of profit from your purchase, while the price remains the same to you. The proceeds from your purchase support our research and work. Thank you for your support.

Takeaway

Phenylalanine builds neurotransmitters and proteins to support your mental health and metabolism. Protein-rich foods such as eggs, cheese, beans, and meat are excellent sources of phenylalanine.

L-phenylalanine may boost your mood, help with vitiligo, and support weight loss. D-phenylalanine may help with chronic pain and addictions. A mixture of these 2 forms, DL-phenylalanine (DLPA) may combat depression and attention disorders.

Supplements are safe for healthy adults. Pregnant women, children, and people taking drugs for Parkinson’s disease should avoid them.

People with phenylketonuria can’t metabolize phenylalanine. They should stay clear of all sources of this amino acid and follow a special low-protein diet.

About the Author

Aleksa Ristic, MSc (Pharmacy)

MS (Pharmacy)

Aleksa received his MS in Pharmacy from the University of Belgrade, his master thesis focusing on protein sources in plant-based diets.

 

Aleksa is passionate about herbal pharmacy, nutrition, and functional medicine. He found a way to merge his two biggest passions—writing and health—and use them for noble purposes. His mission is to bridge the gap between science and everyday life, helping readers improve their health and feel better.

Click here to subscribe

RATE THIS ARTICLE

1 Star2 Stars3 Stars4 Stars5 Stars
(1 votes, average: 5.00 out of 5)
Loading...

FDA Compliance

The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.